Pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF), represents a chronic and progressive disease with high mortality and limited therapeutic options. Pulmonary fibrosis is a chronic lung disease characterized pathologically by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture, and additionally characterized by recognizable clinical, physiologic, and radiographic findings. The pathologic findings in pulmonary fibrosis (excessive accumulation of ECM and remodeling of the lung architecture) are a consequence of disturbances in two physiologically balanced processes: proliferation and apoptosis of fibroblasts, and accumulation and breakdown of ECM. When the normal balance between ECM deposition and turnover is shifted toward deposition or away from breakdown, excessive ECM accumulates. When the balance between fibroblast proliferation and apoptosis is shifted toward accelerated proliferation or slowed apoptosis, fibroblasts accumulate.
IPF is characterized by a poor prognosis, with an estimated 5-year survival of approximately 20%. Subjects suffering from IPF experience progressive and irreversible lung functional impairment that leads to chronic respiratory insufficiency with a severely impaired quality of life. Therefore, there is a continuing need to develop new therapeutic approaches to the treatment of subjects having pulmonary fibrosis, including IPF.